Insights from Experts at Mayo Clinic on Translating Evidence to Clinical Practice - Episode 8

Case Presentation 3: Managing NDMM in Frail Patients

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Moving to the last patient case of newly diagnosed multiple myeloma, expert panelists work together to define patient frailty in this setting and discuss how frail patients are treated in practice.


Shaji Kumar, MD: Prashant, let’s talk about this patient of yours next.

Prashant Kapoor, MD: This patient is a 73-year-old woman whom I saw a few years ago. She had presented with severe back pain and left groin pain and was referred to me for autologous stem cell transplantation approximately a year after her diagnosis of myeloma. At the time I evaluated her, her performance status was 3. She had presented with poor heart function. She was labeled as a case of idiopathic dilated cardiomyopathy with a left ventricular ejection fraction of approximately 30% and had dual chamber ICD [implantable cardioverter defibrillator] implanted. At the time of her initial diagnosis, her hemoglobin was 12 g/dL, calcium was normal, and her creatinine was normal as well. LDH [lactate dehydrogenase] was 177 U/L, beta-2 microglobulin was 3.8 mg/L, albumin was 4 g/dL, and M spike was 3.8 g/dL and it was IgG [immunoglobulin G] Kappa. IgG levels were over 5000 and she had co-existing immunoporosis with low IgA [immunoglobulin A] and IgM [immunoglobulin M] levels. Her free light chain ratio was 98 g/dL, and the 24-hour urine protein electrophoresis did not show any evidence of quantifiable protein. The IFE [immunofixation] was suggestive of a very small Kappa monoclonal protein. When this patient was referred to me, we had already ruled out AL [amyloid light chain] amyloidosis.

When I saw the patient, there was no bone marrow that was available from the time of diagnosis. The treating physician felt that MRI findings were compatible with multiple myeloma so just a sacral biopsy was done, and that sacral lesion biopsy was suggestive of Kappa-restricted plasma cells consistent with the diagnosis of plasmacytoma. Because there were other lesions also present at the time of diagnosis, the patient was treated with, after radiation therapy, lenalidomide [Revlimid] and dexamethasone. When I saw her, she had already attained complete remission, but because of her cardiac function, she was deemed ineligible for autologous stem cell transplant. I discontinued dexamethasone, which she was thankful for, and I advised her to remain on lenalidomide monotherapy. It was only after 3 years since I saw her that her disease progressed, so she remained on lenalidomide for a total of 4 years and Rd [lenalidomide and dexamethasone] for the initial 12 months.

Shaji Kumar, MD: It’s interesting how the heterogeneity affects patient outcomes and here’s a patient who did so well with the triplet. The question is, could she have done even better with the doublet or the triplet? This patient was frail and many of us would start this patient on a doublet, see how the performance improves and maybe add a third drug, and in some situations, we certainly would start these patients off at triplet. There’s data from the MAIA study, as Morie already pointed out. Even sub-groups with frail patients, based on the ECOG performance status and the Charlson Comorbidity Index, obtained a similar benefit with the additional daratumumab [Darzalex], the lenalidomide, and dexamethasone as with the less frail patients. A triplet regimen can be considered for these frail patients whether we start it together or add the third drug after a period of time depending upon how the performance status improves. This brings up the question of frailty as was mentioned. Is that something that you routinely do in the clinic? What instruments would you use?

David Dingli, MD: There’s been a lot of talk about frailty in multiple myeloma and there are 2 ways to do it. One is the eyeball test, and then there are more formal tests. The IMWG [International Myeloma Working Group] came up with a classification for this based on age, performance status and activities of daily living, and the Charlson Comorbidity Index. In general, patients younger than 75 would have a Charlson Comorbidity Index rating of 1 or less. Patients who are fairly independent with activities of daily living are considered not frail. Patients over the age of 80 or with 2 or more of those other characteristics are considered frail. Generally, I do not use these detailed characteristics. One can ask a few questions and use the ECOG performance status. I look at comorbidities and functional status to make decisions. Another important consideration is the social support that the patient has. A patient who has social support with respect to family and relatives who can help the patient is in a much better position than a patient who doesn’t have that type of social support. Sometimes this is neglected.

Shaji Kumar, MD: Frailty is one way we can make modifications to treatment and determine what approaches to use for the risk assessment. Unfortunately, this patient does not have an official from diagnosis. Morie, is there anything else you would factor in when you decide if this a high-risk patient or a standard-risk patient?

Morie Gertz, MD: Risk for myeloma is not just caused by genetics. That’s what we use for trials. That’s what the IMWG uses. But there are so many factors that are not in high risk. You see a patient who shows up with multiple liver lesions, biopsy proven plasmacytoma, proliferative indexes. This is not a part of IMWG, but if those patients have a high proliferative index, it’s going to be bad news. You know about this plasma. Leukemia is not included in the high risk, but if you see patients even with small numbers of circulating cells, you’re nervous about the situation. We use genetic risk for the purpose of a trial stratification, but there are so many others. Simple creatinine is not multivariable, but it’s significant. Like David said, you ask, did you drive yourself to the office or did someone have to drive you? Are you in my office? Did you walk from the parking lot or are you in a wheelchair to come? Those are very relevant questions in determining your pain level and how much opioid you need to control it. Those questions all factor in as to what the patient can safely tolerate.

Transcript edited for clarity.